Adhesions of body tissues occur as the damaged organ surface binds to other tissues during the process of regeneration. In this connection, various kinds of adhesion barriers have been proposed that use biocompatible materials, such as cellulose and other polysaccharides, to prevent postoperative adhesions.
For example, an adhesion barrier using an aqueous solution of carboxymethylcellulose has been proposed (Am. J. Surg., 169, 154-159 (1995)). However, the adhesion barrier described in this publication has poor retention in the body, and cannot exhibit its adhesion barrier effect sufficiently. Accordingly, various attempts have been made to modify the polysaccharides using various methods, or make the polysaccharides water-insoluble.
For example, an adhesion barrier is proposed in which hyaluronic acid and carboxymethyl cellulose are modified with a carbodiimide (International Publication WO92/000105, and International Publication WO92/020349). Further, an adhesion barrier is proposed whose primary component is a cellulose derivative prepared by substituting the hydrogen atoms of cellulose with specific substituents (JP-A-1-301624). An adhesion barrier is also proposed that is formed from a hyaluronic acid compound modified with phosphatidylethanolamine (JP-A-2006-296916).
U.S. Pat. No. 5,064,817 describes obtaining phospholipase A2 inhibiting compositions by the reaction of a low-molecular-weight carboxymethylcellulose with phosphatidylethanolamine in an aqueous solvent. It has been shown, however, that the intended compound cannot be obtained under the conditions of this reaction, as will be described later in Comparative Example 5.
International Publication WO2001/046265 describes a water-insoluble biocompatible gel prepared by the reaction of a polyanionic polysaccharide with an activating agent in an aqueous solution containing a water-miscible organic solvent, using, for example, carboxymethylcellulose as the polyanionic polysaccharide.
However, all of these proposals require further studies in regard to adhesion barrier effect, ease of handling, and safety. As noted above, there has been a suggestion to introduce a phospholipid into cellulose; however, no studies have been made concerning hydrogels that are easy to handle, and have an adhesion barrier effect.
JP-A-9-296005 describes introducing a hydrophobic modifying group to polysaccharides to increase viscosity and improve biostability without gelation of the polysaccharides. However, the publication does not describe or even indicate a cellulose derivative or a cellulose derivative-containing composition, such as that of the present invention, useful to provide the adhesion barrier effect.